The present invention relates to methods of treating immune disorders, particularly autoimmune diseases and cancers having an immune-deficient aspect involving NKG2D-positive CD4+ cells. In addition, the invention provides screening methods that assess the ability of compositions to modulate the negative immunomodulatory effects of NKG2D-positive CD4+ cells. Also provided is a new target for inhibition of signaling by soluble MIC ligand, namely, the ERP-5 disulphide isomerase that interacts with MICA/MICB on the surface of tumor cells.
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